{"gene":"SGO2","run_date":"2026-04-28T20:42:07","timeline":{"discoveries":[{"year":2007,"finding":"hSgo2 (Tripin) localizes to the inner centromere and is required for MCAK localization to the centromere; depletion of hSgo2 causes MCAK delocalization, leading to uncorrected kinetochore attachment errors and lagging chromosomes. hSgo2 localization depends on BUB1 and Aurora B kinases, and it redistributes toward kinetochores under tension. hSgo2 is also associated with PP2A.","method":"siRNA depletion, immunofluorescence localization, Co-IP (hSgo2–PP2A association), live-cell imaging of kinetochore attachment defects","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 — reciprocal Co-IP, clean KD with defined cellular phenotype (lagging chromosomes, MCAK mislocalization), replicated by subsequent studies","pmids":["17485487"],"is_preprint":false},{"year":2007,"finding":"During male mouse meiosis, SGO2 accumulates at centromeres during diplotene/metaphase I and colocalizes with cohesin subunits RAD21 and REC8. SGO2 shows tension-dependent redistribution within centromeres during meiosis II and mitosis, suggesting it can unmask cohesive centromere proteins for release or separase cleavage.","method":"Immunofluorescence localization in mouse meiotic/mitotic cells; co-localization with cohesin subunits","journal":"EMBO reports","confidence":"Medium","confidence_rationale":"Tier 3 — direct localization experiment with functional model proposed, single lab","pmids":["17205076"],"is_preprint":false},{"year":2010,"finding":"Aurora B kinase phosphorylates hSgo2 at N-terminal coiled-coil and middle regions; these phosphorylations separately promote binding of hSgo2 to PP2A (required for centromeric protection of cohesion) and to MCAK (required for chromosome congression), and are essential for localizing PP2A and MCAK to centromeres in HeLa cells.","method":"In vitro kinase assay (Aurora B phosphorylating hSgo2), phosphomutant analysis, Co-IP (hSgo2–PP2A and hSgo2–MCAK), siRNA depletion with rescue experiments, immunofluorescence","journal":"Genes & development","confidence":"High","confidence_rationale":"Tier 1-2 — in vitro kinase assay plus phosphomutant rescue plus Co-IP, moderate evidence from multiple orthogonal methods in single study","pmids":["20889715"],"is_preprint":false},{"year":2010,"finding":"In aged mouse oocytes, depletion of Sgo2 accompanies loss of centromeric cohesin; Sgo2 protects centromeric cohesin during meiosis I, and its decline contributes to age-related chromosome missegregation.","method":"Immunostaining of cohesin and Sgo2 in oocytes from young vs. aged wild-type mice; quantification of chromosome segregation fidelity","journal":"Current biology : CB","confidence":"Medium","confidence_rationale":"Tier 3 — direct localization with correlation to functional outcome; single lab but highly cited","pmids":["20817533"],"is_preprint":false},{"year":2013,"finding":"In mouse oocytes, Sgol2 protects centromeric cohesin via interaction with PP2A; it also silences the SAC via direct binding to Mad2, promotes bivalent congression and K-fiber formation by recruiting MCAK, and limits bivalent stretching independently of PP2A by inhibiting Aurora C kinase activity.","method":"Genetic KO/depletion in oocytes, epistasis experiments, Co-IP (Sgol2–PP2A, Sgol2–Mad2, Sgol2–MCAK), functional rescue assays","journal":"eLife","confidence":"High","confidence_rationale":"Tier 2 — KO with defined phenotypes plus multiple Co-IPs and epistasis in single study with multiple orthogonal methods","pmids":["24192037"],"is_preprint":false},{"year":2017,"finding":"Mps1 kinase activity is required for Sgo2 localization to the centromere region in mouse oocyte meiosis I, and this centromeric Sgo2 is essential for centromeric cohesin protection. Bub1 kinase activity (which phosphorylates H2A-T121) localizes Sgo2 preferentially to the pericentromere but is dispensable for cohesin protection when Mps1 is functional.","method":"Mps1 inhibitor treatment of oocytes, Bub1 kinase-dead mutant oocytes, Sgo2 localization by immunofluorescence, cohesin protection assay","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 — genetic/pharmacological epistasis with direct localization and functional readout (cohesin protection), multiple perturbations","pmids":["28947820"],"is_preprint":false},{"year":2017,"finding":"In fission yeast, Sgo2 mediates a Mad2-independent, APC/C-inhibitory pathway that delays anaphase onset when the chromosome passenger complex (CPC) cannot interact with Klp9/MKLP2; this pathway requires Sgo2 and some SAC components (Bub1, Mps1/Mph1, Mad3) but not Mad1 or Mad2, and depends on the first KEN box of Mad3.","method":"Genetic epistasis in fission yeast; double-mutant analysis; deletion of SAC components in Klp9-interaction-defective background","journal":"Cell reports","confidence":"Medium","confidence_rationale":"Tier 2 — genetic epistasis with defined pathway placement; single organism (fission yeast ortholog)","pmids":["28178520"],"is_preprint":false},{"year":2019,"finding":"SET/TAF1 localizes to the inner centromere by directly interacting with SGO2, where it maintains Aurora B kinase activity by inhibiting PP2A, thereby correcting erroneous kinetochore-microtubule attachments. SET levels at centromeres inversely correlate with kinetochore pair distance (tension), and SET overexpression causes chromosomal instability.","method":"Co-IP (SET–SGO2 direct interaction), immunofluorescence localization, SET overexpression/knockdown with chromosomal instability readout","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2-3 — Co-IP plus functional KD/OE phenotype; single lab, moderate evidence","pmids":["31527146"],"is_preprint":false},{"year":2022,"finding":"SGOL2 interacts with RAB1A in a protein–protein manner and inhibits RAB1A ubiquitination, thereby stabilizing RAB1A protein levels and promoting prostate cancer cell proliferation and migration.","method":"Mass spectrometry, Co-IP (SGOL2–RAB1A interaction), ubiquitination assay, rescue experiments in prostate cancer cell lines","journal":"Aging","confidence":"Low","confidence_rationale":"Tier 3 — Co-IP and ubiquitination assay; single lab, single study, cancer context with limited mechanistic depth","pmids":["36566018"],"is_preprint":false},{"year":2025,"finding":"SGO2 does not play an essential role in inhibiting separase during meiosis I in mouse oocytes; securin or cyclin B1-CDK1 each independently provide sufficient separase inhibition, and SGO2 destruction does not correlate with an essential separase-inhibitory function in this context.","method":"Separase biosensor in mouse oocytes, genetic perturbation of securin, cyclin B1-CDK1, and SGO2 inhibitory pathways; SGO2 destruction dynamics","journal":"PLoS biology","confidence":"High","confidence_rationale":"Tier 1-2 — biosensor assay plus multiple genetic perturbations with orthogonal readouts; single study but rigorous design","pmids":["40267054"],"is_preprint":false},{"year":2025,"finding":"In hybrid mouse oocytes (Mus musculus domesticus × Mus spicilegus), elevated BUB1 kinase activity causes SGO2 mis-localization to chromosome arms instead of centromeres, leading to cohesin over-protection and failure of homologous chromosome separation in meiosis I.","method":"Hybrid mouse crosses, immunofluorescence localization of SGO2 and BUB1 in oocytes, BUB1 kinase activity assay, aneuploidy quantification","journal":"bioRxiv (preprint)","confidence":"Medium","confidence_rationale":"Tier 2 — direct localization with functional consequence plus kinase activity measurement; preprint, single lab","pmids":[],"is_preprint":true},{"year":2025,"finding":"In fission yeast, Sgo2 relocalizes from centromeres to subtelomeres during interphase to establish knob chromatin structure; this subtelomeric localization depends on histone H4 deacetylation by the Nts1 complex and H3-K36 methylation by Set2, acting redundantly downstream of H2A-S121 phosphorylation.","method":"Genetic screen in fission yeast, deletion of nts1+ and set2+, immunofluorescence of Sgo2, histone modification analysis","journal":"iScience","confidence":"Medium","confidence_rationale":"Tier 2 — genetic screen plus epistasis and direct localization; fission yeast ortholog, single lab","pmids":["40520116"],"is_preprint":false}],"current_model":"SGO2 is a conserved centromeric protein that protects centromeric cohesin during meiosis (via recruitment of PP2A) and in perturbed mitosis; its functions are orchestrated by Aurora B-mediated phosphorylation, which separately promotes SGO2 binding to PP2A (for cohesin protection) and to MCAK (for error correction of kinetochore attachments and chromosome congression), while Mps1 and Bub1 kinases regulate its centromeric localization; additionally, SGO2 scaffolds SET/TAF1 at the inner centromere to balance Aurora B and PP2A activities, directly binds Mad2 to silence the spindle assembly checkpoint, and recruits MCAK to correct improper kinetochore–microtubule attachments, but is dispensable for separase inhibition in mouse oocyte meiosis I."},"narrative":{"teleology":[{"year":2007,"claim":"Establishing that SGO2 is an inner-centromere protein required for MCAK recruitment and kinetochore attachment error correction answered where SGO2 acts and what happens when it is absent — lagging chromosomes and MCAK delocalization.","evidence":"siRNA depletion, immunofluorescence, Co-IP with PP2A, and live-cell imaging in HeLa cells","pmids":["17485487"],"confidence":"High","gaps":["Mechanism by which SGO2 recruits MCAK not resolved","Whether PP2A association is functionally required not tested","Upstream signals controlling SGO2 centromeric localization unknown"]},{"year":2007,"claim":"Demonstrating that SGO2 colocalizes with centromeric cohesin subunits RAD21 and REC8 and redistributes under tension in mouse meiosis established it as a candidate cohesin protector in mammalian meiosis.","evidence":"Immunofluorescence co-localization in mouse spermatocytes and oocytes","pmids":["17205076"],"confidence":"Medium","gaps":["No loss-of-function evidence for cohesin protection provided","Mechanism of tension-dependent redistribution unknown"]},{"year":2010,"claim":"Identifying Aurora B as the kinase that phosphorylates SGO2 at separate sites to independently control PP2A binding (cohesin protection) and MCAK binding (error correction) resolved how one scaffold coordinates two distinct centromeric functions through differential phosphorylation.","evidence":"In vitro kinase assay, phosphomutant rescue, Co-IP in HeLa cells","pmids":["20889715"],"confidence":"High","gaps":["Structural basis of phospho-dependent binding switches unknown","Whether additional kinases contribute not tested"]},{"year":2010,"claim":"Correlating age-related decline of Sgo2 at centromeres with cohesin loss and chromosome missegregation in aged mouse oocytes provided a physiological context — maternal age-related aneuploidy — for SGO2's cohesin protection function.","evidence":"Immunostaining and quantification in oocytes from young versus aged mice","pmids":["20817533"],"confidence":"Medium","gaps":["Causal rescue experiment (restoring Sgo2 in aged oocytes) not performed","Whether decline is transcriptional or post-translational not determined"]},{"year":2013,"claim":"Genetic knockout in mouse oocytes demonstrated that Sgol2 simultaneously protects cohesin (via PP2A), silences the SAC (via direct Mad2 binding), promotes congression (via MCAK), and limits bivalent stretching (by inhibiting Aurora C), establishing it as a multi-arm centromeric coordinator during female meiosis.","evidence":"Genetic KO in oocytes, Co-IP for PP2A/Mad2/MCAK, epistasis and functional rescue","pmids":["24192037"],"confidence":"High","gaps":["How SGO2–Mad2 interaction silences the SAC mechanistically is unclear","Relative contribution of Aurora C inhibition versus other arms not quantified"]},{"year":2017,"claim":"Pharmacological and genetic dissection of Mps1 and Bub1 kinase requirements revealed that Mps1 is essential for centromeric SGO2 localization and cohesin protection, while Bub1-mediated H2A phosphorylation directs SGO2 to the pericentromere but is not required for cohesin protection when Mps1 is active.","evidence":"Mps1 inhibitor and Bub1 kinase-dead mutant oocytes with SGO2 immunofluorescence and cohesin protection assay","pmids":["28947820"],"confidence":"High","gaps":["Direct Mps1 substrate on SGO2 or loading factor not identified","Whether this hierarchy applies in mitotic cells not tested"]},{"year":2017,"claim":"In fission yeast, identification of a Mad2-independent, Sgo2-dependent APC/C-inhibitory pathway revealed that SGO2 orthologs can delay anaphase onset through a non-canonical checkpoint mechanism when CPC–Klp9 interaction is disrupted.","evidence":"Double-mutant genetic epistasis in S. pombe","pmids":["28178520"],"confidence":"Medium","gaps":["Whether this pathway operates in mammalian cells is untested","Biochemical mechanism of APC/C inhibition by Sgo2 not determined"]},{"year":2019,"claim":"Showing that SET/TAF1 is recruited to the inner centromere through direct interaction with SGO2, where SET sustains Aurora B activity by locally inhibiting PP2A, revealed a positive-feedback loop through which SGO2 balances Aurora B and PP2A at centromeres.","evidence":"Co-IP of SET–SGO2, SET knockdown/overexpression with chromosomal instability readout in HeLa cells","pmids":["31527146"],"confidence":"Medium","gaps":["Structural basis of SET–SGO2 interaction not resolved","How tension regulates SET displacement not mechanistically clear"]},{"year":2025,"claim":"Biosensor experiments in mouse oocytes established that SGO2 is dispensable for separase inhibition during meiosis I, with securin and cyclin B1–CDK1 each providing sufficient inhibition independently, resolving a long-standing question about whether SGO2 has a direct separase-inhibitory role.","evidence":"Separase biosensor plus genetic perturbation of securin, cyclin B1–CDK1, and SGO2 in mouse oocytes","pmids":["40267054"],"confidence":"High","gaps":["Whether SGO2 contributes to separase regulation in meiosis II or mitosis not addressed","Mechanism of SGO2 destruction timing still unexplored"]},{"year":2025,"claim":"Discovery that fission yeast Sgo2 relocalizes from centromeres to subtelomeres during interphase to establish knob chromatin, dependent on histone H4 deacetylation and H3-K36 methylation, revealed an unexpected non-mitotic chromatin-organizing function for SGO2 orthologs.","evidence":"Genetic screen, nts1/set2 deletion, immunofluorescence and histone modification analysis in S. pombe","pmids":["40520116"],"confidence":"Medium","gaps":["Whether mammalian SGO2 has analogous interphase chromatin roles is unknown","Molecular mechanism of knob formation not determined"]},{"year":null,"claim":"Key unresolved questions include the structural basis of SGO2's multi-partner scaffolding (PP2A, MCAK, Mad2, SET), the direct Mps1 substrate or adaptor that loads SGO2 to centromeres, whether the non-canonical SAC-inhibitory pathway operates in mammals, and whether SGO2 has interphase chromatin functions outside yeast.","evidence":"","pmids":[],"confidence":"Low","gaps":["No high-resolution structure of SGO2 or its complexes","Direct Mps1-dependent loading mechanism unresolved","Mammalian relevance of interphase chromatin role untested"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,2,4,7]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[4,7]}],"localization":[{"term_id":"GO:0005694","term_label":"chromosome","supporting_discovery_ids":[0,1,2,5,11]}],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[0,2,4,5,9]},{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[11]}],"complexes":[],"partners":["PP2A","MCAK","MAD2","AURB","BUB1","SET","MPS1"],"other_free_text":[]},"mechanistic_narrative":"SGO2 is a conserved inner-centromere protein that serves as a multifunctional scaffold coordinating cohesin protection, kinetochore–microtubule error correction, and spindle assembly checkpoint (SAC) signaling during cell division. Aurora B kinase phosphorylates SGO2 at distinct sites to separately promote its binding to PP2A, which protects centromeric cohesin, and to MCAK, which corrects erroneous kinetochore attachments and supports chromosome congression; centromeric localization of SGO2 itself requires Mps1 kinase activity, while Bub1-mediated H2A phosphorylation directs SGO2 preferentially to the pericentromere [PMID:20889715, PMID:28947820, PMID:17485487]. SGO2 additionally recruits SET/TAF1 to the inner centromere to sustain Aurora B activity by locally inhibiting PP2A, directly binds Mad2 to silence the SAC, and in fission yeast participates in a Mad2-independent APC/C-inhibitory pathway, yet is dispensable for separase inhibition during mouse oocyte meiosis I [PMID:31527146, PMID:24192037, PMID:28178520, PMID:40267054]. Beyond mitosis and meiosis, fission yeast Sgo2 relocalizes to subtelomeres during interphase to establish knob chromatin structure in a manner dependent on histone deacetylation and H3-K36 methylation [PMID:40520116]."},"prefetch_data":{"uniprot":{"accession":"Q562F6","full_name":"Shugoshin 2","aliases":["Shugoshin-2","Shugoshin-like 2","Tripin"],"length_aa":1265,"mass_kda":144.7,"function":"Cooperates with PPP2CA to protect centromeric cohesin from separase-mediated cleavage in oocytes specifically during meiosis I. Has a crucial role in protecting REC8 at centromeres from cleavage by separase. During meiosis, protects centromeric cohesion complexes until metaphase II/anaphase II transition, preventing premature release of meiosis-specific REC8 cohesin complexes from anaphase I centromeres. Is thus essential for an accurate gametogenesis. May act by targeting PPP2CA to centromeres, thus leading to cohesin dephosphorylation (By similarity). Essential for recruiting KIF2C to the inner centromere and for correcting defective kinetochore attachments. Involved in centromeric enrichment of AUKRB in prometaphase","subcellular_location":"Nucleus; Chromosome, centromere; Chromosome, centromere, kinetochore","url":"https://www.uniprot.org/uniprotkb/Q562F6/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SGO2","classification":"Not Classified","n_dependent_lines":76,"n_total_lines":1208,"dependency_fraction":0.06291390728476821},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CAPZB","stoichiometry":0.2},{"gene":"HSPA4","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/SGO2","total_profiled":1310},"omim":[{"mim_id":"616232","title":"MEIOTIC KINETOCHORE FACTOR; MEIKIN","url":"https://www.omim.org/entry/616232"},{"mim_id":"612425","title":"SHUGOSHIN-LIKE 2; SGOL2","url":"https://www.omim.org/entry/612425"},{"mim_id":"609168","title":"SHUGOSHIN-LIKE 1; SGOL1","url":"https://www.omim.org/entry/609168"},{"mim_id":"176915","title":"PROTEIN PHOSPHATASE 2, CATALYTIC SUBUNIT, ALPHA ISOFORM; PPP2CA","url":"https://www.omim.org/entry/176915"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Nucleoplasm","reliability":"Enhanced"},{"location":"Nuclear bodies","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"lymphoid tissue","ntpm":13.9},{"tissue":"testis","ntpm":30.5}],"url":"https://www.proteinatlas.org/search/SGO2"},"hgnc":{"alias_symbol":["TRIPIN","FLJ25211"],"prev_symbol":["SGOL2"]},"alphafold":{"accession":"Q562F6","domains":[],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q562F6","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q562F6-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q562F6-F1-predicted_aligned_error_v6.png","plddt_mean":42.78},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SGO2","jax_strain_url":"https://www.jax.org/strain/search?query=SGO2"},"sequence":{"accession":"Q562F6","fasta_url":"https://rest.uniprot.org/uniprotkb/Q562F6.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q562F6/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q562F6"}},"corpus_meta":[{"pmid":"20817533","id":"PMC_20817533","title":"Age-related meiotic segregation errors in mammalian oocytes are preceded by depletion of cohesin and Sgo2.","date":"2010","source":"Current biology : CB","url":"https://pubmed.ncbi.nlm.nih.gov/20817533","citation_count":285,"is_preprint":false},{"pmid":"17485487","id":"PMC_17485487","title":"Tripin/hSgo2 recruits MCAK to the inner centromere to correct defective kinetochore attachments.","date":"2007","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/17485487","citation_count":115,"is_preprint":false},{"pmid":"20889715","id":"PMC_20889715","title":"Phosphorylation of mammalian Sgo2 by Aurora B recruits PP2A and MCAK to centromeres.","date":"2010","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/20889715","citation_count":112,"is_preprint":false},{"pmid":"17205076","id":"PMC_17205076","title":"Mammalian SGO2 appears at the inner centromere domain and redistributes depending on tension across centromeres during meiosis II and mitosis.","date":"2007","source":"EMBO reports","url":"https://pubmed.ncbi.nlm.nih.gov/17205076","citation_count":73,"is_preprint":false},{"pmid":"24192037","id":"PMC_24192037","title":"Sgol2 provides a regulatory platform that coordinates essential cell cycle processes during meiosis I in oocytes.","date":"2013","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/24192037","citation_count":66,"is_preprint":false},{"pmid":"28947820","id":"PMC_28947820","title":"Mps1 kinase-dependent Sgo2 centromere localisation mediates cohesin protection in mouse oocyte meiosis I.","date":"2017","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/28947820","citation_count":55,"is_preprint":false},{"pmid":"32275843","id":"PMC_32275843","title":"CDK1-PLK1/SGOL2/ANLN pathway mediating abnormal cell division in cell cycle may be a critical process in hepatocellular carcinoma.","date":"2020","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/32275843","citation_count":34,"is_preprint":false},{"pmid":"23884434","id":"PMC_23884434","title":"SGO1 but not SGO2 is required for maintenance of centromere cohesion in Arabidopsis thaliana meiosis.","date":"2013","source":"Plant reproduction","url":"https://pubmed.ncbi.nlm.nih.gov/23884434","citation_count":30,"is_preprint":false},{"pmid":"28178520","id":"PMC_28178520","title":"Identification of a Sgo2-Dependent but Mad2-Independent Pathway Controlling Anaphase Onset in Fission Yeast.","date":"2017","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/28178520","citation_count":15,"is_preprint":false},{"pmid":"31527146","id":"PMC_31527146","title":"Aurora B kinase activity is regulated by SET/TAF1 on Sgo2 at the inner centromere.","date":"2019","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/31527146","citation_count":14,"is_preprint":false},{"pmid":"36566018","id":"PMC_36566018","title":"SGOL2 promotes prostate cancer progression by inhibiting RAB1A ubiquitination.","date":"2022","source":"Aging","url":"https://pubmed.ncbi.nlm.nih.gov/36566018","citation_count":7,"is_preprint":false},{"pmid":"40267054","id":"PMC_40267054","title":"SGO2 does not play an essential role in separase inhibition during meiosis I in mouse oocytes.","date":"2025","source":"PLoS biology","url":"https://pubmed.ncbi.nlm.nih.gov/40267054","citation_count":3,"is_preprint":false},{"pmid":"40520116","id":"PMC_40520116","title":"Histone deacetylation as a landmark for Sgo2 relocation from centromeres to subtelomeres during interphase.","date":"2025","source":"iScience","url":"https://pubmed.ncbi.nlm.nih.gov/40520116","citation_count":0,"is_preprint":false},{"pmid":"41340734","id":"PMC_41340734","title":"Comprehensive Analysis and Experimental Validation of Single-Cell and Transcriptome Sequencing Reveal SGO2 as a Novel Biomarker for Breast Cancer.","date":"2025","source":"Breast cancer (Dove Medical 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mouse oocytes","date":"2025-01-06","source":"bioRxiv","url":"https://doi.org/10.1101/2025.01.06.631516","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.10.03.616439","title":"Subtelomere-specific condensed chromatin is regulated by three different histone modifications","date":"2024-10-04","source":"bioRxiv","url":"https://doi.org/10.1101/2024.10.03.616439","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.10.27.684817","title":"Replication-competent SIVcpz CRISPR screen identifies barriers to successful cross-species transmission","date":"2025-10-27","source":"bioRxiv","url":"https://doi.org/10.1101/2025.10.27.684817","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.02.11.637638","title":"Elimination of separase inhibition reveals absence of cohesin protection in oocyte metaphase II","date":"2025-02-12","source":"bioRxiv","url":"https://doi.org/10.1101/2025.02.11.637638","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":10381,"output_tokens":2992,"usd":0.038011},"stage2":{"model":"claude-opus-4-6","input_tokens":6363,"output_tokens":2642,"usd":0.146797},"total_usd":0.184808,"stage1_batch_id":"msgbatch_011rkcQdVV1RaFq9XhcG6df6","stage2_batch_id":"msgbatch_01RzgrJafdF4EWHhj5mNi6dh","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2007,\n      \"finding\": \"hSgo2 (Tripin) localizes to the inner centromere and is required for MCAK localization to the centromere; depletion of hSgo2 causes MCAK delocalization, leading to uncorrected kinetochore attachment errors and lagging chromosomes. hSgo2 localization depends on BUB1 and Aurora B kinases, and it redistributes toward kinetochores under tension. hSgo2 is also associated with PP2A.\",\n      \"method\": \"siRNA depletion, immunofluorescence localization, Co-IP (hSgo2–PP2A association), live-cell imaging of kinetochore attachment defects\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP, clean KD with defined cellular phenotype (lagging chromosomes, MCAK mislocalization), replicated by subsequent studies\",\n      \"pmids\": [\"17485487\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"During male mouse meiosis, SGO2 accumulates at centromeres during diplotene/metaphase I and colocalizes with cohesin subunits RAD21 and REC8. SGO2 shows tension-dependent redistribution within centromeres during meiosis II and mitosis, suggesting it can unmask cohesive centromere proteins for release or separase cleavage.\",\n      \"method\": \"Immunofluorescence localization in mouse meiotic/mitotic cells; co-localization with cohesin subunits\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — direct localization experiment with functional model proposed, single lab\",\n      \"pmids\": [\"17205076\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Aurora B kinase phosphorylates hSgo2 at N-terminal coiled-coil and middle regions; these phosphorylations separately promote binding of hSgo2 to PP2A (required for centromeric protection of cohesion) and to MCAK (required for chromosome congression), and are essential for localizing PP2A and MCAK to centromeres in HeLa cells.\",\n      \"method\": \"In vitro kinase assay (Aurora B phosphorylating hSgo2), phosphomutant analysis, Co-IP (hSgo2–PP2A and hSgo2–MCAK), siRNA depletion with rescue experiments, immunofluorescence\",\n      \"journal\": \"Genes & development\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — in vitro kinase assay plus phosphomutant rescue plus Co-IP, moderate evidence from multiple orthogonal methods in single study\",\n      \"pmids\": [\"20889715\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"In aged mouse oocytes, depletion of Sgo2 accompanies loss of centromeric cohesin; Sgo2 protects centromeric cohesin during meiosis I, and its decline contributes to age-related chromosome missegregation.\",\n      \"method\": \"Immunostaining of cohesin and Sgo2 in oocytes from young vs. aged wild-type mice; quantification of chromosome segregation fidelity\",\n      \"journal\": \"Current biology : CB\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — direct localization with correlation to functional outcome; single lab but highly cited\",\n      \"pmids\": [\"20817533\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"In mouse oocytes, Sgol2 protects centromeric cohesin via interaction with PP2A; it also silences the SAC via direct binding to Mad2, promotes bivalent congression and K-fiber formation by recruiting MCAK, and limits bivalent stretching independently of PP2A by inhibiting Aurora C kinase activity.\",\n      \"method\": \"Genetic KO/depletion in oocytes, epistasis experiments, Co-IP (Sgol2–PP2A, Sgol2–Mad2, Sgol2–MCAK), functional rescue assays\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — KO with defined phenotypes plus multiple Co-IPs and epistasis in single study with multiple orthogonal methods\",\n      \"pmids\": [\"24192037\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Mps1 kinase activity is required for Sgo2 localization to the centromere region in mouse oocyte meiosis I, and this centromeric Sgo2 is essential for centromeric cohesin protection. Bub1 kinase activity (which phosphorylates H2A-T121) localizes Sgo2 preferentially to the pericentromere but is dispensable for cohesin protection when Mps1 is functional.\",\n      \"method\": \"Mps1 inhibitor treatment of oocytes, Bub1 kinase-dead mutant oocytes, Sgo2 localization by immunofluorescence, cohesin protection assay\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic/pharmacological epistasis with direct localization and functional readout (cohesin protection), multiple perturbations\",\n      \"pmids\": [\"28947820\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"In fission yeast, Sgo2 mediates a Mad2-independent, APC/C-inhibitory pathway that delays anaphase onset when the chromosome passenger complex (CPC) cannot interact with Klp9/MKLP2; this pathway requires Sgo2 and some SAC components (Bub1, Mps1/Mph1, Mad3) but not Mad1 or Mad2, and depends on the first KEN box of Mad3.\",\n      \"method\": \"Genetic epistasis in fission yeast; double-mutant analysis; deletion of SAC components in Klp9-interaction-defective background\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genetic epistasis with defined pathway placement; single organism (fission yeast ortholog)\",\n      \"pmids\": [\"28178520\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"SET/TAF1 localizes to the inner centromere by directly interacting with SGO2, where it maintains Aurora B kinase activity by inhibiting PP2A, thereby correcting erroneous kinetochore-microtubule attachments. SET levels at centromeres inversely correlate with kinetochore pair distance (tension), and SET overexpression causes chromosomal instability.\",\n      \"method\": \"Co-IP (SET–SGO2 direct interaction), immunofluorescence localization, SET overexpression/knockdown with chromosomal instability readout\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — Co-IP plus functional KD/OE phenotype; single lab, moderate evidence\",\n      \"pmids\": [\"31527146\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"SGOL2 interacts with RAB1A in a protein–protein manner and inhibits RAB1A ubiquitination, thereby stabilizing RAB1A protein levels and promoting prostate cancer cell proliferation and migration.\",\n      \"method\": \"Mass spectrometry, Co-IP (SGOL2–RAB1A interaction), ubiquitination assay, rescue experiments in prostate cancer cell lines\",\n      \"journal\": \"Aging\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — Co-IP and ubiquitination assay; single lab, single study, cancer context with limited mechanistic depth\",\n      \"pmids\": [\"36566018\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"SGO2 does not play an essential role in inhibiting separase during meiosis I in mouse oocytes; securin or cyclin B1-CDK1 each independently provide sufficient separase inhibition, and SGO2 destruction does not correlate with an essential separase-inhibitory function in this context.\",\n      \"method\": \"Separase biosensor in mouse oocytes, genetic perturbation of securin, cyclin B1-CDK1, and SGO2 inhibitory pathways; SGO2 destruction dynamics\",\n      \"journal\": \"PLoS biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — biosensor assay plus multiple genetic perturbations with orthogonal readouts; single study but rigorous design\",\n      \"pmids\": [\"40267054\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In hybrid mouse oocytes (Mus musculus domesticus × Mus spicilegus), elevated BUB1 kinase activity causes SGO2 mis-localization to chromosome arms instead of centromeres, leading to cohesin over-protection and failure of homologous chromosome separation in meiosis I.\",\n      \"method\": \"Hybrid mouse crosses, immunofluorescence localization of SGO2 and BUB1 in oocytes, BUB1 kinase activity assay, aneuploidy quantification\",\n      \"journal\": \"bioRxiv (preprint)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct localization with functional consequence plus kinase activity measurement; preprint, single lab\",\n      \"pmids\": [],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In fission yeast, Sgo2 relocalizes from centromeres to subtelomeres during interphase to establish knob chromatin structure; this subtelomeric localization depends on histone H4 deacetylation by the Nts1 complex and H3-K36 methylation by Set2, acting redundantly downstream of H2A-S121 phosphorylation.\",\n      \"method\": \"Genetic screen in fission yeast, deletion of nts1+ and set2+, immunofluorescence of Sgo2, histone modification analysis\",\n      \"journal\": \"iScience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genetic screen plus epistasis and direct localization; fission yeast ortholog, single lab\",\n      \"pmids\": [\"40520116\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SGO2 is a conserved centromeric protein that protects centromeric cohesin during meiosis (via recruitment of PP2A) and in perturbed mitosis; its functions are orchestrated by Aurora B-mediated phosphorylation, which separately promotes SGO2 binding to PP2A (for cohesin protection) and to MCAK (for error correction of kinetochore attachments and chromosome congression), while Mps1 and Bub1 kinases regulate its centromeric localization; additionally, SGO2 scaffolds SET/TAF1 at the inner centromere to balance Aurora B and PP2A activities, directly binds Mad2 to silence the spindle assembly checkpoint, and recruits MCAK to correct improper kinetochore–microtubule attachments, but is dispensable for separase inhibition in mouse oocyte meiosis I.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"SGO2 is a conserved inner-centromere protein that serves as a multifunctional scaffold coordinating cohesin protection, kinetochore–microtubule error correction, and spindle assembly checkpoint (SAC) signaling during cell division. Aurora B kinase phosphorylates SGO2 at distinct sites to separately promote its binding to PP2A, which protects centromeric cohesin, and to MCAK, which corrects erroneous kinetochore attachments and supports chromosome congression; centromeric localization of SGO2 itself requires Mps1 kinase activity, while Bub1-mediated H2A phosphorylation directs SGO2 preferentially to the pericentromere [PMID:20889715, PMID:28947820, PMID:17485487]. SGO2 additionally recruits SET/TAF1 to the inner centromere to sustain Aurora B activity by locally inhibiting PP2A, directly binds Mad2 to silence the SAC, and in fission yeast participates in a Mad2-independent APC/C-inhibitory pathway, yet is dispensable for separase inhibition during mouse oocyte meiosis I [PMID:31527146, PMID:24192037, PMID:28178520, PMID:40267054]. Beyond mitosis and meiosis, fission yeast Sgo2 relocalizes to subtelomeres during interphase to establish knob chromatin structure in a manner dependent on histone deacetylation and H3-K36 methylation [PMID:40520116].\",\n  \"teleology\": [\n    {\n      \"year\": 2007,\n      \"claim\": \"Establishing that SGO2 is an inner-centromere protein required for MCAK recruitment and kinetochore attachment error correction answered where SGO2 acts and what happens when it is absent — lagging chromosomes and MCAK delocalization.\",\n      \"evidence\": \"siRNA depletion, immunofluorescence, Co-IP with PP2A, and live-cell imaging in HeLa cells\",\n      \"pmids\": [\"17485487\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism by which SGO2 recruits MCAK not resolved\", \"Whether PP2A association is functionally required not tested\", \"Upstream signals controlling SGO2 centromeric localization unknown\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Demonstrating that SGO2 colocalizes with centromeric cohesin subunits RAD21 and REC8 and redistributes under tension in mouse meiosis established it as a candidate cohesin protector in mammalian meiosis.\",\n      \"evidence\": \"Immunofluorescence co-localization in mouse spermatocytes and oocytes\",\n      \"pmids\": [\"17205076\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No loss-of-function evidence for cohesin protection provided\", \"Mechanism of tension-dependent redistribution unknown\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Identifying Aurora B as the kinase that phosphorylates SGO2 at separate sites to independently control PP2A binding (cohesin protection) and MCAK binding (error correction) resolved how one scaffold coordinates two distinct centromeric functions through differential phosphorylation.\",\n      \"evidence\": \"In vitro kinase assay, phosphomutant rescue, Co-IP in HeLa cells\",\n      \"pmids\": [\"20889715\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of phospho-dependent binding switches unknown\", \"Whether additional kinases contribute not tested\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Correlating age-related decline of Sgo2 at centromeres with cohesin loss and chromosome missegregation in aged mouse oocytes provided a physiological context — maternal age-related aneuploidy — for SGO2's cohesin protection function.\",\n      \"evidence\": \"Immunostaining and quantification in oocytes from young versus aged mice\",\n      \"pmids\": [\"20817533\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Causal rescue experiment (restoring Sgo2 in aged oocytes) not performed\", \"Whether decline is transcriptional or post-translational not determined\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Genetic knockout in mouse oocytes demonstrated that Sgol2 simultaneously protects cohesin (via PP2A), silences the SAC (via direct Mad2 binding), promotes congression (via MCAK), and limits bivalent stretching (by inhibiting Aurora C), establishing it as a multi-arm centromeric coordinator during female meiosis.\",\n      \"evidence\": \"Genetic KO in oocytes, Co-IP for PP2A/Mad2/MCAK, epistasis and functional rescue\",\n      \"pmids\": [\"24192037\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How SGO2–Mad2 interaction silences the SAC mechanistically is unclear\", \"Relative contribution of Aurora C inhibition versus other arms not quantified\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Pharmacological and genetic dissection of Mps1 and Bub1 kinase requirements revealed that Mps1 is essential for centromeric SGO2 localization and cohesin protection, while Bub1-mediated H2A phosphorylation directs SGO2 to the pericentromere but is not required for cohesin protection when Mps1 is active.\",\n      \"evidence\": \"Mps1 inhibitor and Bub1 kinase-dead mutant oocytes with SGO2 immunofluorescence and cohesin protection assay\",\n      \"pmids\": [\"28947820\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct Mps1 substrate on SGO2 or loading factor not identified\", \"Whether this hierarchy applies in mitotic cells not tested\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"In fission yeast, identification of a Mad2-independent, Sgo2-dependent APC/C-inhibitory pathway revealed that SGO2 orthologs can delay anaphase onset through a non-canonical checkpoint mechanism when CPC–Klp9 interaction is disrupted.\",\n      \"evidence\": \"Double-mutant genetic epistasis in S. pombe\",\n      \"pmids\": [\"28178520\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether this pathway operates in mammalian cells is untested\", \"Biochemical mechanism of APC/C inhibition by Sgo2 not determined\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Showing that SET/TAF1 is recruited to the inner centromere through direct interaction with SGO2, where SET sustains Aurora B activity by locally inhibiting PP2A, revealed a positive-feedback loop through which SGO2 balances Aurora B and PP2A at centromeres.\",\n      \"evidence\": \"Co-IP of SET–SGO2, SET knockdown/overexpression with chromosomal instability readout in HeLa cells\",\n      \"pmids\": [\"31527146\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Structural basis of SET–SGO2 interaction not resolved\", \"How tension regulates SET displacement not mechanistically clear\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Biosensor experiments in mouse oocytes established that SGO2 is dispensable for separase inhibition during meiosis I, with securin and cyclin B1–CDK1 each providing sufficient inhibition independently, resolving a long-standing question about whether SGO2 has a direct separase-inhibitory role.\",\n      \"evidence\": \"Separase biosensor plus genetic perturbation of securin, cyclin B1–CDK1, and SGO2 in mouse oocytes\",\n      \"pmids\": [\"40267054\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether SGO2 contributes to separase regulation in meiosis II or mitosis not addressed\", \"Mechanism of SGO2 destruction timing still unexplored\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Discovery that fission yeast Sgo2 relocalizes from centromeres to subtelomeres during interphase to establish knob chromatin, dependent on histone H4 deacetylation and H3-K36 methylation, revealed an unexpected non-mitotic chromatin-organizing function for SGO2 orthologs.\",\n      \"evidence\": \"Genetic screen, nts1/set2 deletion, immunofluorescence and histone modification analysis in S. pombe\",\n      \"pmids\": [\"40520116\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether mammalian SGO2 has analogous interphase chromatin roles is unknown\", \"Molecular mechanism of knob formation not determined\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key unresolved questions include the structural basis of SGO2's multi-partner scaffolding (PP2A, MCAK, Mad2, SET), the direct Mps1 substrate or adaptor that loads SGO2 to centromeres, whether the non-canonical SAC-inhibitory pathway operates in mammals, and whether SGO2 has interphase chromatin functions outside yeast.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No high-resolution structure of SGO2 or its complexes\", \"Direct Mps1-dependent loading mechanism unresolved\", \"Mammalian relevance of interphase chromatin role untested\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 2, 4, 7]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [4, 7]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005694\", \"supporting_discovery_ids\": [0, 1, 2, 5, 11]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [0, 2, 4, 5, 9]},\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [11]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"PP2A\", \"MCAK\", \"MAD2\", \"AURB\", \"BUB1\", \"SET\", \"MPS1\"],\n    \"other_free_text\": []\n  }\n}\n```"}